Mucin is a glycoprotein in which a core protein is modified with a high-molecular-weight sugar chain. The high-molecular-weight sugar chain is a macromolecule having 100 to 10 million of the molecular weight. Mucin is found as a sticky substance in the mucosal membrane of the oral cavity, respiratory tract, stomach, or intestinal tract of an animal, and protects a tender mucosal membrane in an inner cavity that is in contact with the outside, from pathogens, foreign substances, drying, and the like. Twenty-one kinds of mucin are known in humans, and core proteins of each of the mucin molecules have different repeat sequences. The region of the repeat amino acid sequence contains an abundance of serine and threonine, and a mucin-type sugar chain is bound thereto in high frequency. The mucin-type sugar chain is generally composed of N-acetyl galactosamine, N-acetyl glucosamine, galactose, fucose, sialic acid, or the like. The sugar chain contributes 50 to 80% or more of the molecular weight of mucin, and is a cause of diverse properties of mucin, such as stickiness, water retention ability, resistance to a protein degrading enzymes and the like.
Among the mucins, MUC5AC has a repeat sequence that is abundant in serine and threonine as a core protein. In normal tissue, MUC5AC is expressed only in epithelial cells of the trachea or stomach. Regarding the relationship of the MUC5AC and diseases, it is known that MUC5AC is expressed in cancer tissue. In particular, it is reported that MUC5AC, which is a membrane-binding type mucin, is expressed at a high rate in association with canceration of the pancreas (Non-patent literatures 1 and 2). In addition, it is reported that excessive secretion of MUC5AC in the respiratory tract leads to aggravation of asthma in patients with asthma (Non-patent literature 3).
Pancreatic cancer is known as a refractory cancer. In 2000, the number of patients with cancer of the pancreas was 17,000 in Japan, and 30,000 in the US. The number of pancreatic cancer patients is predicted to increase. Pancreatic cancer patients do not make up a large proportion of cancer patients. However, the degree of malignancy, which is a number of age-adjusted death rate divided with age-adjusted cancer rate, of pancreatic cancer was the highest among all cancers in 1998. That is, the degree of malignancy was 99.2% for men and 94.6% for women. In addition, the 5-year-survival rate of the pancreatic cancer patients is very low (approximately 10%) in both men and women, which means that pancreatic cancer is a refractory cancer having a poor prognosis.
A current standard therapy for pancreatic cancer is surgery. That is, in the case of early diagnosis, removal of tumor site is considered to be an effective therapy. However, pancreatic cancer has few symptoms, and so diagnosis of early lesions (1 cm or less) using an endoscope or diagnostic imaging is difficult. Furthermore, a tumor marker specific to pancreatic cancer does not exist. Therefore, it is difficult to detect pancreatic cancer in its early stages, and only about 30% of cases allow operation. For advanced-staged pancreatic cancer, a chemical therapy is mainly conducted. In particular, gemcitabine (nucleic acid synthesis inhibitor, Eli Lilly Japan K.K.) is used. However, this only has symptom alleviation effects, and has no fundamental therapeutic effects on the tumor. Sometimes, a radiation therapy is combined with the surgical therapy. However, pancreatic cancer has low sensitivity to radiation, and this therapy is not effective. Therefore, it is desirable to develop an effectual pharmaceutical composition capable of suppressing the proliferation of tumor cells and improving the QOL in pancreatic cancer patients.
As described above, MUC5AC is expressed at a high rate in tissue of pancreatic cancer. However, it is reported that lymph invasion, blood vessel invasion, and lymph node metastasis are found in pancreatic cancer patients having no expression of MUC5AC, and therefore, the survival rate is better in pancreatic cancer patients having MUC5AC expression (Non-patent literature 1). Accordingly, from a viewpoint of the survival rate of pancreatic cancer patients, it is preferable that MUC5AC is expressed in pancreatic cancer.